Inclusion Criteria:

1. Patients with histologically confirmed intrahepatic, perihilar or extra-hepatic CCA.
2. Patients with no more than 2 prior treatments with systemic anti-neoplastic therapy for CCA.
3. The tumor is unresectable and not amenable to curative therapy.
4. One or more tumors measurable on CT scan per RECIST 1.1.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0- 1.
6. Life expectancy of at least 3 months.
7. Age ≥18 years.
8. Signed, written IRB-approved informed consent.
9. A negative pregnancy test (if female).
10. Acceptable liver and renal function:
    • Bilirubin ≤ 1.5 times upper limit of normal (CTCAE Grade 2 baseline)
    • AST (SGOT), ALT (SGPT) ≤ 2.5 x upper limit of normal (ULN),
    • Serum creatinine ≤ 1.5 X ULN (CTCAE Grade 1 baseline)
    • Albumin > 3.0 g/dL
11. Acceptable hematologic status:
    • Absolute neutrophil count ≥1000 cells/mm3
    • Platelet count ≥75,000 (plt/mm3) (CTCAE Grade 1 baseline)
    • Hemoglobin ≥ 9 g/dL
12. Acceptable blood sugar control
    • Fasting glucose value ≤ 160 mg/dL (CTCAE Grade 1 baseline)
13. Urinalysis: No clinically significant abnormalities.
14. Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.5 X ULN after correction of nutritional deficiencies that may have contributed to prolonged PT/PTT.
15. For men and women of child-producing potential, willingness to use effective contraceptive methods during the study. If female (or female partner of male patient), was either not of childbearing potential (defined as postmenopausal for ≥ 1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy or hysterectomy]) or practicing one of the following medically acceptable methods of birth control and agreed to continue with the regimen throughout the duration of the study:
    • Oral, implantable or injectable contraceptives for 3 consecutive months before the baseline/randomization visit.
    • Total abstinence from sexual intercourse (≥ 1 complete menstrual cycle before the baseline/randomization visit).
    • Intrauterine device.
    • Double barrier method (condoms, sponge, diaphragm or vaginal ring with spermicidal jellies or cream

Exclusion Criteria:

1. >2 previous systemic anti-neoplastic regimens for CCA.
2. New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG.
3. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
4. Pregnant or nursing women. NOTE: If a woman became pregnant or suspects she is pregnant while participating in this study, she must inform her treating physician immediately.
5. Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within 28 days prior to study entry.
6. Patients who have received any antineoplastic therapy > 28 days prior to starting treatment with ABC294640 and have not adequately recovered from side effects and toxicities of previous antineoplastic therapy.
7. Unwillingness or inability to comply with procedures required in this protocol.
8. Known infection with human immunodeficiency virus.
9. Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor.
10. Patients who were currently receiving any other investigational agent.
11. Patients who were receiving drugs that were sensitive substrates of CYP450 1A2, 3A4, 2C9, 2C19 or 2D6, or strong inhibitors or inducers of all major CYP450 isozymes that could not have been stopped at least 7 days or 5 half-lives (whichever was longer) before starting treatment with ABC294640, could not have been replaced with another appropriate medication or not given for the duration of the clinical study. (A list of commonly used drugs that are sensitive substrates of CYP450 1A2, 3A4, 2C9, 2C19 or 2D6, or strong inhibitors or inducers of all major CYP450 isozymes with the half-life of each drug identified, is included in Appendix 3)
12. Patients who are taking Coumadin or Coumadin derivatives.